Astragalin Attenuates Bone Destruction and the Progression of Bone Metastasis in Breast Cancer

Background: Bone metastasis of breast Cancer (BC) is a key reason for poor prognosis. Recently, natural ingredients derived from Plants have been found to exert a broad anti-tumor effect and are considered to be promising candidates for Adjuvant therapy. Astragalin (AS) was found to inhibit the progression of several types of tumors; however, the role of AS in regulating the bone metastasis of BC is still unclear. Methods: The effects of AS on the progression of bone metastasis of BC were detected in vivo through safranin O and fast green staining, in vivo living imaging and microCT. The BrdU assay and Annexin V-PI analysis were used to detect the effects of AS on the growth of BC cells. Furthermore, TRAP staining was performed to examine the formation of osteoclasts regulated by AS. A transcriptome was performed to explore the downstream effects of AS on regulating the growth of BC cells, and the mechanism was further confirmed by Western blot and Real-Time PCR. Results: Administration of AS could effectively attenuate the bone destruction and the progression of bone metastasis of BC. The growth of BC cells can be inhibited by AS by inducing ER stress-mediated upregulation of Ddit3. In addition, AS can also prevent osteoclastogenesis through inhibiting the activation of the Akt pathway. Conclusions: Our studies suggest that AS could be an ideal Adjuvant therapy for attenuating the progression of bone metastasis of BC, since it can directly restrict the growth of tumor, as well as attenuate osteolysis.

astragalin; bone metastasis; breast cancer; osteoclastogenesis.